AI Article Synopsis
- VLGR1 (ADGRV1) is the largest member of the adhesion GPCR family, with mutations linked to Usher syndrome and childhood absence epilepsy.
- Research shows VLGR1 interacts with proteins associated with the endoplasmic reticulum (ER) and mitochondria, particularly at mitochondria-associated ER membranes (MAMs).
- Studies using various assays confirmed that VLGR1 is crucial for maintaining MAM structure and regulating calcium (Ca) homeostasis between the ER and mitochondria.
Article Abstract
The very large G protein-coupled receptor (VLGR1, ADGRV1) is the largest member of the adhesion GPCR family. Mutations in VLGR1 have been associated with the human Usher syndrome (USH), the most common form of inherited deaf-blindness as well as childhood absence epilepsy. VLGR1 was previously found as membrane-membrane adhesion complexes and focal adhesions. Affinity proteomics revealed that in the interactome of VLGR1, molecules are enriched that are associated with both the ER and mitochondria, as well as mitochondria-associated ER membranes (MAMs), a compartment at the contact sites of both organelles. We confirmed the interaction of VLGR1 with key proteins of MAMs by pull-down assays in vitro complemented by in situ proximity ligation assays in cells. Immunocytochemistry by light and electron microscopy demonstrated the localization of VLGR1 in MAMs. The absence of VLGR1 in tissues and cells derived from VLGR1-deficient mouse models resulted in alterations in the MAM architecture and in the dysregulation of the Ca transient from ER to mitochondria. Our data demonstrate the molecular and functional interaction of VLGR1 with components in MAMs and point to an essential role of VLGR1 in the regulation of Ca homeostasis, one of the key functions of MAMs.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496679 | PMC |
| http://dx.doi.org/10.3390/cells11182790 | DOI Listing |
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